化学
SKBR3型
上皮-间质转换
癌症研究
乳腺癌
受体酪氨酸激酶
癌症
细胞迁移
MTT法
癌细胞
酪氨酸激酶
细胞生长
受体
细胞
过渡(遗传学)
生物化学
生物
内科学
医学
人体乳房
基因
作者
Xinyang Li,Xin-hua Qian,Jü Zhu,Yuheng Li,Qi-qi Lin,Shuai Li,Wen-han Xue,Lingyan Jian,Fan‐hao Meng
标识
DOI:10.1016/j.ejmech.2022.114325
摘要
Human epidermal growth factor receptor 2 (HER-2) is an essential member of the receptor tyrosine kinase (RTK) superfamily and has been reported as a critical method for treating HER-2 positive breast cancer. Here, we retained (E)-4-methyl-2-(4-(trifluoromethyl)styryl)oxazole, a fragment of HER-2 inhibitor Mubritinib, and synthesized 32 novel compounds from it. We screened out the most potential compound Q7j with HER-2 positive breast cancer cells through MTT assays, which possessed low toxicity on normal cells (MCF7-10A). Subsequently, wound healing, transwell, western blotting, and immunofluorescence experiments were performed, and it was found that compound Q7j could suppress cell migration by inhibiting the phosphorylation of HER-2 and affecting the expression of EMT-related proteins. Moreover, the SKBR3 orthotopic xenograft model confirmed that compound Q7j was more effective than Mubritinib in inhibiting the proliferation of cancer cells. In general, compound Q7j was a potential HER-2 inhibitor in treating breast cancer, which may be of great significance for developing and improving HER-2 small molecule inhibitors.
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